Human circulating fibrocytes have the capacity to differentiate osteoblasts and chondrocytes

Abstract

Fibrocytes are bone marrow-derived cells. Fibrocytes can differentiate into adipocyte- and myofibroblast-like cells. Since fibrocytes can behave like mesenchymal progenitor cells, we hypothesized that fibrocytes have the potential to differentiate into other mesenchymal lineage cells, such as osteoblasts and chondrocytes. In this study, we found that fibrocytes differentiated into osteoblast-like cells when cultured in osteogenic media in a manner similar to osteoblast precursor cells. Under these conditions, fibrocytes and osteoblast precursor cells displayed increased calcium deposition, and increased expression of specific osteogenic genes. In addition, dephosphorylation of cAMP-responsive element binding protein was associated with the increased ratio of receptor activator of the NF-kappaB Ligand/osteoprotegerin gene expression and enhanced gene expression of osterix in these cells under these conditions. Both events are important in promoting osteogenesis. In contrast, fibrocytes and mesenchymal stem cells cultured in chondrogenic media in the presence of transforming growth factor-beta3 were found to differentiate to chondrocyte-like cells. Fibrocytes and mesenchymal stem cells under these conditions were found to express increased levels of aggrecan and type II collagen genes. Transcription factor genes associated with chondrogenesis were also found to be induced in fibrocytes and mesenchymal stem cells under these conditions. In contrast, beta-catenin protein and the core binding factor alpha1 subunit protein transcription factor were decreased in expression under these conditions. These data indicate that human fibrocytes have the capability to differentiate into osteoblast- and chondrocyte-like cells. These findings suggest that such cells could be used in cell-based tissue-regenerative therapy.